Leukaemia

Question 1

What is the definition of acute lymphoblastic leukaemia?

Answer 1

Malignant disease of primitive lymphoid cells (lymphoblasts).

Question 2

Who does ALL most typically affect?

Answer 2

Most common childhood cancer (peaks age 2-4)
Can affect adults over 45
Often associated with Down syndrome

Question 3

What is the pathophysiology of ALL?

Answer 3

Malignant change in one of the lymphocyte precursor cells causing acute proliferation of a single type of lymphocyte (usually B lymphocytes)
Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to pancytopenia

Question 4

What are some clinical features of ALL?

Answer 4

Marrow failure - anaemia, infections, bleeding
Leukaemic effects - high count with obstruction of circulation
Involvement of areas outside the marrow and blood (extramedullary) eg CNS, testis
Bone pain

Question 5

What are some investigations for ALL?

Answer 5

Blood count and film:
- Reduction in normal cells
- Presence of blasts (large size, high nuclear:cytoplasmic ratio, prominent nucleus)

Coagulation screen

Bone marrow aspirate:
- Morphology
- Immunophenotype
- Cyto/molecular genetics
- Trephine

Question 6

What is the management of ALL?

Answer 6

Multi-agent chemotherapy for 2-3 years
CNS targeted treatment
Hickman line used for long term central venous access

Question 7

What are some complications of ALL and AML disease?

Answer 7

Anaemia
Neutropenia (gram negative bacteria and fungal infections)
Thrombocytopenia (bleeding, purpura, petechiae)

Question 8

What are some complications of ALL and AML treatment?

Answer 8

Nausea and vomiting
Hair loss
Liver and renal dysfunction
Infection
Late effects: loss of fertility, cardiomyopathy

Question 9

What is the definition of acute myeloid leukaemia?

Answer 9

Malignant disease of the primitive myeloid cells (progenitor cell for granulocytes, monocytes, erythrocytes or platelets).

Question 10

Who does AML typically affect?

Answer 10

Elderly (>60 years)
Often associated with myelodysplastic syndromes but can arise ‘de novo’

Question 11

What are some clinical features of AML?

Answer 11

Marrow failure: anaemia, infections, bleeding
Subgroups characteristic presentation
- Coagulation defect/DIC in acute promyelocytic leukaemia
- Gum infiltration in acute monocytic leukaemia and acute myelomonocytic leukaemia

Question 12

What are some investigations of AML?

Answer 12

Blood count and film:
- Reduction in normal size
- Presence of blasts (large size, high nuclear:cytoplasmic ratio, prominent nucleolus)
- Auer rods inside blast cell cytoplasm

Coagulation screen

Bone marrow aspirate:
- Morphology
- Immunophenotype
- Cyto/molecular genetics
- Trephine

Question 13

What is the management of AML?

Answer 13

Multi-agent chemotherapy
- 2-4 cycles
- Prolonged hospitalisation
- Targeted treatments in subsets
- Hickman line used for long-term venous access

Question 14

What is the definition of chronic myeloid leukaemia?

Answer 14

Malignant proliferation of primitive myeloid cells (granulocytes and their precursors and other lineages eg platelets) with preserved maturation

Question 15

What is the genetic mutation involved in CML?

Answer 15

Philadelphia chromosome
Translocation between chromosome 9 and 22, t(9:22), resulting in new gene BCR-ABL1
BCR-ABL1 is a tyrosine kinase and causes abnormal phosphorylation leading to haematological changes in CML

Question 16

What are the three phases of CML?

Answer 16

Chronic:
- Lasts around 5 years, often asymptomatic, diagnosed with incidental raised WBC

Accelerated:
- More symptomatic with anaemia, thrombocytopenia, immunocompromised, 10-20% proportion of blast cells in marrow and blood

Blast:
- Severe symptoms and pancytopenia, often fatal, >30% proportion of blast cells in marrow and blood

Question 17

What are some clinical features of CML?

Answer 17

Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout (high cell turnover causes high urate)
Others: hyperleucocytosis, priapism

Question 18

What are some investigations for CML?

Answer 18

FBC:
- Normal or decreased Hb
- Increased WBC
- Low/normal/raised platelets

Blood film:
- Neutrophilia with myeloid precursors and blasts

Leucocyte alkaline phosphate (LAP):
- Usually reduced

Bone marrow biopsy:
- Not usually done but would show increased cellularity

Genetics:
-FISH used for cytogenic abnormality in bone marrow or blood

Question 19

What is the management of CML?

Answer 19

Stem cell/bone marrow transplant in chronic phase (fatal without)
Tyrosine kinase inhibitors (imatinib)

Question 20

What is the definition of chronic lymphocytic leukaemia?

Answer 20

Chronic proliferation of a single type of well differentiated/less primitive lymphocyte (usually B lymphocytes).

Question 21

Who does CLL typically affect?

Answer 21

Adults over 55

Question 22

What are some symptoms of CLL?

Answer 22

Often asymptomatic
Infections, anaemia, bleeding, weight loss
Warm autoimmune haemolytic anaemia

Question 23

What are some investigations for CLL?

Answer 23

Blood count:
- Hb normal or low
- Increased WBCs
- Normal or low platelets

Blood film:
- Increased lymphocytes (>5x109/L)
- ‘Smear’ or ‘smudge’ cells

Bone marrow:
- Immunophenotyping (mainly CD19/20 and CD5 B cells)
- Cytogenetics (deletion of 13q most common, trisomy 12)

Question 24

What is the management of CLL?

Answer 24

Chemo not usually need in early stage disease
Absolute indications for treatment:
- Weight loss >10% over 6 months
- Night sweats lasting >1 month
- Progressive marrow failure

Question 25

What are some complications of CLL?

Answer 25

Can transform into high-grade lymphoma